Effect of choline chloride based natural deep eutectic solvents on aqueous solubility and thermodynamic properties of acetaminophen

• Published in: Journal of molecular liquids 2021-02, Vol.323, p.114834, Article 114834
• Main Authors: Warmińska, Dorota, Nowosielski, Bartosz, Szewczyk, Adrian, Ruszkowski, Jakub, Prokopowicz, Magdalena
• Format: Article
• Language: English
• Subjects: Acetaminophen; Deep eutectic solvents; Solubility; Thermodynamic properties
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2020.114834

In this work, natural deep eutectic solvents (NADESs) containing choline chloride as hydrogen bond acceptor and 1,2-propanediol, malic acid and tartaric acid as hydrogen bond donors have been synthesized and applied to enhance the aqueous solubility of model sparingly water-soluble drug – acetaminophen. The results indicate that the greatest impact on the solubility of acetaminophen have deep eutectic solvents based on 1,2-propanediol or malic acid and the solubility of acetaminophen increases with both the concentration of NADES and temperature. Among the Apelblat, λh (Buchowski-Ksiazczak), Yalkowsky and combined Jouyban–Acree and van ‘t Hoff models correlating the solubility data, the Apelblat model is more consistent with the experimental data. Moreover, densities and sound velocities of acetaminophen in aqueous NADESs were measured at T = (298.15–313.15) K and these data were used to derive the limiting apparent molar volumes and the apparent molar compressibilities of the transfer. The thermodynamic properties show that the hydrophilic-ionic and hydrophilic-hydrophilic interactions in solutions of acetaminophen are predominant and this effect is the strongest for acetaminophen in aqueous choline chloride:malic acid solution. •Three choline chloride-based natural deep eutectic solvents (NADES) were obtained.•The NADES were investigated as co-solvents that enhancing acetaminophen solubility.•The modified Apelblat equation was the most accurate thermodynamic solubility model.•Acetaminophen can be considered as a structure maker in obtained NADESs solutions.•Drug-NADES interactions were defined as hydrophilic-ionic, hydrophilic-hydrophilic.